Monday, May 22, 2017

Abstract

The
split of our own clade from the Panini is undocumented in the fossil
record. To fill this gap we investigated the dentognathic morphology of Graecopithecus freybergi from Pyrgos Vassilissis (Greece) and cf. Graecopithecus
sp. from Azmaka (Bulgaria), using new μCT and 3D reconstructions of the
two known specimens. Pyrgos Vassilissis and Azmaka are currently dated
to the early Messinian at 7.175 Ma and 7.24 Ma. Mainly based on its
external preservation and the previously vague dating, Graecopithecus
is often referred to as nomen dubium. The examination of its previously
unknown dental root and pulp canal morphology confirms the taxonomic
distinction from the significantly older northern Greek hominine Ouranopithecus. Furthermore, it shows features that point to a possible phylogenetic affinity with hominins. G. freybergi
uniquely shares p4 partial root fusion and a possible canine root
reduction with this tribe and therefore, provides intriguing evidence of
what could be the oldest known hominin.

...

In this study, we propose based on root morphology a new possible candidate for the hominin clade, Graecopithecus freybergi from Europe. Graecopithecus is known from a single mandible from Pyrgos Vassilissis Amalia (Athens, Greece) [38] and possibly from an isolated upper fourth premolar (P4) from Azmaka in Bulgaria [39] (Fig 1A and 1B).
A new age model for the localities Pyrgos Vassilissis and Azmaka, as
well as the investigations on the fauna of these localities [40]
confirms that European hominids thrived in the early Messinian (Late
Miocene, 7.25–6 Ma) and therefore existed in Europe ~ 1.5 Ma later than
previously thought [39].
This, and recent discoveries from Çorakyerler (Turkey), and Maragheh
(Iran) demonstrate the persistence of Miocene hominids into the Turolian
(~8 Ma) in Europe, the eastern Mediterranean, and Western Asia [41, 42].

Monday, May 1, 2017

Today, I obtained genotype data comprising MCM6 SNPs from HapMapfor
2436 individuals from 26 HapMap populations (ESN, GWD, LWK, MSL, YRI,
ACB, ASW, CLM, MXL, PEL, PUR, CDX, CHB, CHS, FIN, GBR, IBS, TSI, CEU,
BEB, ITU, JPT, KHV, PJL, STU, GIH). Haplotype annotation of each individual can be downloaded here. I focused on all the SNPs that show
more variation (more than 1% of the alternative base). I excluded all
SNPs that have varying numbers of bases (insertion/deletion), and I
excluded rs4988274 and rs55809728 because they did not show a clear
pattern (hypervariability?). I excluded all haplotypes that were only
present in 2 or less individuals. Using the remaining 203 SNPs I was
able to identify 76 haplogroups. Please note that there are many more
haplotypes (especially in Africa); I just focused on most common ones as
stated above. Please also note that I changed the nomenclature at this stage because the following three reasons:1. Some of the populations identified in Enattah et al., 2008 are not present in the HapMap dataset. Thus, some of the identified haplotypes in Enattah et al., 2008 are missing here.2. Because this time I used more SNPs most of the haplotypes split into several haplotypes:
ht1=> ht17-30 (blue)
ht2=> ht31 (turquoise)
ht3=> ht32 (turquoise)
ht4=> ht59-73 (orange)
ht5=> ht74-76 (red)
ht6=> ht49-57 (green)
ht13=> ht46-48 (brown)
ht16=> ht45 (cayenne)

I also checked the data of Denisova and Neanderthals for these 203 SNPs, and predicted the missing SNPs.

Find below the phylogenetic tree of the 76 MCM6 haplotypes including Denisova and Neanderthals.

SNPs of 76 haplotypes including the Denisova and Neanderthal SNPs (predicted ones in grey) and frequencies of all 76 haplogroups can be downloaded here (with summary at bottom).

Distribution of the main branches of MCM6:

Every branch of the phylogenetic tree of MCM6 tells its migration story. Based on the generated data I will try to postulate the steps of these migrations.

Grey branch (Denisova/Neanderthals/previous and current ht5):ht5 is derived from the Denisova genome. The
frequency of the ht5 suggests that the admixture Denisova and our
ancestors occurred in Asia, which is in accordance with the current
state of scientific knowledge.

Green branch (ht49-57; previously ht6):

Africa: ht50 is the ancestor of this green branch, and is only found in individuals with African ancestry (7-16%). ht50 was not part of OOA (Out of Africa). The alternative hypothesis would be that ht50 derived from ht52.
ht51
is derived from ht52 and is only present in Africans and Afro-Americans
(2% in Gambians, 0.8% African Ancestry in Southwest US). OOA:
ht52 is derived from ht50 and can be found in Africa (1-4%) and all
parts of Eurasia. It is especially common in East Asia (12-21%). ht52 was part of OOA. ht52 split into two groups, one that kept staying in Eastern Eurasia and one that moved to Western Eurasia.Eastern Eurasia:
ht53 is derived from ht52 and can not be found in Africa (no back
migration to Africa), but it can be found in Eastern Eurasia, especially
South Asians (2-8%) and East Asians (4-5%), and made it into native
Americans (11% in Peruvians). Given its very low frequencies in Southern
Europe and its lack in Africa I assume that it very rare in the Middle
East.Western Eurasia: ht56 is also derived from
ht52 and can be found in Western Eurasia. ht56 is the most successful ht
among the green branch (ht6) reaching 2-5% in Africa, 2-15% in
Americans (probably through European ancestry because lowest level found
in Peruvians and highest in Colombians and Puerto Ricans), 1-18% in
South Asia, and 10-30% in Europe. It is basically not present in East
Asia (0-1%).
ht54, ht55, and ht57 are derived from ht56 and show a
similar world wide distribution with ht57 being the most successful.
They show no migration to Africa.
ht54 can be found in Europe (0-1%) and South
Asia (0-1%).
ht55 can be found in Europe (1-2%), South Asia
(0-4%), East Asia (0-1%), and Americans (0-1%; probably through European
ancestry because found in Colombians and Puerto Ricans but not found in
Peruvians)
ht57 can be found in Europe (2-5%), South Asia (0-2%),
and Americans (1-5%; probably through European ancestry because lowest
level found in Peruvians and highest in Colombians and Puerto Ricans).
ht49
emerged after a crossing-over event between ht56 and ht18, ht20-ht32
(most likely ht29). Thus, its position in the phylogenetic tree is
misleading.
For Kurds, I expect ht56 and ht52 to be the most
common ones among this branch. If there is any unknown LP persistance
genotype among Kurds then it is probably a subbranch of ht52 or ht56.
Unfortunately, 23andme do not help to distinguish between the hts of the
green branch (ht6).

Blue branch (ht17-30; previously ht1):

ht21 is the ancestor of this blue branch. ht21 can only be found in Africans (0-3%) and Afro-Americans (0-1%).
ht22 is derived from ht21. ht22 can only be found in Africans (0-3%) and Afro-Americans (0-1%).
ht23
is derived from ht22. ht23 can only be found in Africans (2-5%),
Afro-Americans (2-4%), and Americans (0-1%), probably through African
ancestry. OOA: ht29 is derived from ht21. ht29 can be
found in all parts of the world: in Africans (2-6%), in native Americans
(3-10%; not through European ancestry because highest levels found in
Peruvians and Mexicans), in East Asians (24-42%), in South Asians
(4-15%), and in Europeans (1-4%).
Five subbranches are derived from ht29: a) ht24, b) ht25, c) ht26, d) ht28, and e) ht30.
a) ht24 is present in individuals from Southern Europe (0-1%) and Afro-Americans (0-1%).
b) ht25 is only present in South Asia (0-1%).
c) ht26 is present in Europe (0-1%) und South Asia (0-1%).
d) ht28 is only present in East Asia (3-12%).
e)
ht30 is present in native Americans (6-12%; probably not through
European ancestry because the highest levels are found in Peruvians and
Mexicans), in Europeans (1-13%; North-South gradient=British 1% and
Toscana 13%), and in South Asians (3-9%).
ht18 emerged after a crossing-over event between ht29 and ht49-53, ht56,
or ht57. Similar to ht49 in the green branch (ht6), its position in the
phylogenetic tree is misleading.Turquoise branch (ht31-ht32; previously ht2-ht3):
ht31 (ht2) is derived
from ht30. ht31 is very rare but plays a key role for the European
lactase persistence (ht3). As mentioned above, I showed that it is
present in Kurds (2.5%), Iraqi Jews (4.7%), Pakistanis (2-6%), Kalash
(14%), and Arabs from the Middle East (2,5%). Now, I could also confirm
its presence in Americans (0-2%; through Lebanese ancestry?), Toscana
(1%), and South Asians (1%).
ht32 (ht3) is derived from ht31, and is the most frequent MCM6 genotype reaching 71% in Northern Europe and only 8% in Toscana. ht32 is responsible for European lactase persistence
but it can be found elsewhere, too: frequencies of 11-31% in Americans
(through European ancestry because the lowest levels are found in
Peruvians), and 5-25% in South Asians (Northwest/SouthEast gradient with
Punjabis being the highest and Tamils being the lowest). As mentioned
above, I showed that it is present in Kurds (5%), Iranians (5%),
Ob-Ugrics (5%), Arabs from Iraq, Syria, Lebanon and Palestine (13%),
Morocco (17%), Saharawi (23%), and Fulani Sudanese (33%).

Orange branch (ht59-73; previously ht4):

ht61 is the ancestor of the orange branch. ht61 can only be found in South Asia.
ht62
is derived from ht61. ht62 can be found in Africa (1-3%), in Europe
(0-2%), and in South Asia (0-3%). In South Asia there is a North/South
gradient: in Europe the distribution is less clear.
ht63 is derived from ht62 and is solely African (0-1%).
ht64 is derived from ht63 and is also solely African (1-6%).
ht69
is derived from ht62 and is basically African, too (1-4%). Three
subbranches emerged from ht69: a) ht70-71, b) ht65-68, and c) ht74-76
(red branch ht5).
a) ht70 is rare in Africa (0-1%), high among
native Americans (5-22%) and South Asians (8-16%). 1-5% of Europeans
(North/South gradient) and 8-13% of East Asians have ht70.
ht71 is derived from ht70, and is only present in South Asia (3-5%).
b) ht65-68 are all solely African (together 6-12%).
c) ht74-76 is the red branch (ht5; see below)
ht60
emerged after a crossing-over event between ht18, ht28-30, or ht31 and
ht62, hg36-40 or ht69. Similar to ht49 in the green branch (ht6) and
ht18 in the blue branch (ht1), its position in the
phylogenetic tree is misleading.

Red branch (ht74-76; previously ht5):
ht75
is the ancestor of the red branch and can be found in all parts of the
world: 1-4% in Africans, 6-10% in Americans, 7-10% East Asians, 3-14%
in Europeans (North/South gradient), and 7-9% in South Asians. Two
subbranches emerged from ht75: a) ht76 and b) ht74 -40
a) ht76 is
derived from ht75 and is present especially in Native Americans 3-13%
(not through European ancestry because the highest levels are found in
Peruvians and Mexicans), it is also present in Europe 0-2%, and South
Asians 0-3% but not in Africans and East Asians.
b) ht74 and hg40
are derived from ht75 and are basically only present in South Asians
(1-6%) with a clear North/South gradient. ht72 was a little bit more
successful and made it to South Asians (1-3%), East Asians (0-3%),
Europeans (1-3%), and especially in Native Americans 1-7% (not through
European ancestry because the highest levels are found in Peruvians and
Mexicans).

Brown branch (ht46-48; previously ht13):
hg28
is the ancestor of the brown branch and is solely African (0-2%) as
well as all of its derived subbranches ht47, hg30, and ht48.
hg27 emerged after a crossing-over event between hg28 and hg20-21 or hg23-25. Similar to ht49 in the green branch
(ht6), ht18 in the blue branch (ht1), and ht60 in the orange branch (ht4), its position in the
phylogenetic tree is misleading.

The remaining
branches (hg1-25) are mostly African. Exceptions are hg5 (see grey
branch), hg18-19 (0-6% in East Asians), and hg13 (1-2% in South Asians,
0-1% in Europeans and East Asians).

Yellow branch (ht40-44):

ht43 is the ancestor of the yellow branch. The yellow branch is solely African.

I used genetic data from Enattah et al., 2008 and identified 9 SNP of MCM6 that are also tested at 23andme. Based on these 9 SNPs I identified ht1-6, the Saudi-Arabian lactase persistence (ht8), the East African lactase persistence (ht13), and several more. You can download the table here.

In the table above it becomes obvious that Saudi-Arabian lactase
persistence (ht8) is derived from ht5, both share "C" at rs4988243. The European lactase persistence (ht3) is derived from ht2, and the East African lactase persistence (ht15) is derived from ht1.

The European T(-13910) and the earlier identified East African G(-13907)
LP allele share the same ancestral background and most likely the same
history, probably related to the same cattle domestication event. In
contrast, the compound Arab allele shows a different, highly divergent
ancestral haplotype, suggesting that these two major global LP alleles
have arisen independently, the latter perhaps in response to camel milk
consumption. These results support the convergent evolution of the LP in
diverse populations, most probably reflecting different histories of
adaptation to milk culture.

Previously, I showed that Kurds, Iraqi Jews and Pakistanis have ht2.
Now, I could show that ht2 is also present in Arabs from the Middle East
and the Kalash. I determined frequencies of these haplotypes based on
data from Enattah et al., 2008.
I also added the Kurdish data to this table. You can download the table here:

In Eurasia, the vast majority are ht1 to ht6. In Africa, the MCM6 gene is more diverse.
Not surprisingly, Kurds show similarities with Iranians in their MCM6 repertoire and frequencies.

Since these haplotypes are just based on 9 SNPs they are less reliable, I decided to expand the number of SNPs gradually. To define further SNPs of the Saudi-Arabian lactase persistence I asked several Saudi-Arabians to participate in a small survey. I could confirm that the Saudi-Arabian lactase
persistence (ht8) is derived from ht5 and correlates with the expected phenotype (=lactose tolerant). I also observed ht13 in one individual and added both data (ht8 and ht13) in the expanded list of SNPs that can be checked on 23andme. The other haplotypes are extracted (ht9-12, ht14-18) are extracted from Enattah et al., 2008.

Friday, June 12, 2015

A new paper in Nature (Allentoft et al., 2015) presenting the genomes of ancient 101 Eurasians is currently fascinating geneticists but also linguists and historians. Some of these tested Bronze Age individuals lived in nowadays Armenia.

Here, I want to use their Dodecad K12b values (shared by Mfa from Corduene.blogspot.com) to calculate the closest reference populations for these individuals. Most of the tested individuals from Armenia can be resembled the best as 50-75% Iranian (including Kurds) or Lezgin and 25-50% European. In most cases, Kurds and especially Zaza are among the Top10 reference populations for these ancient genomes, see data below.

In terms of genetic composition the Southern Caucasus was more Iranian-like and European-like than it is today. The shift from Bronze Age to now could be explained by several Semitic empires and three Semitic religions (Judaism, Christianity and Islam) that expanded from South to North and probably impacted local populations of the Northern Middle East.

Interestingly, when traveling through Kurdistan a phenotypic gradient can be seen depending on the altitude: populations from hidden villages in the higher Mountains appear to have lighter skin (and lighter eye color) than the populations from towns in the valleys. Kurds also claim that in ancient times their people were more fair-skinned than they are today.

I believe the same (more Iranian-like and European-like than it is today) will be seen for genomes from Kurdistan. I also believe that the European-like character South of the Caucasus was introduced before the Neolithic expansion, hopefully, ancient DNA will prove this one day. As I mentioned earlier I believe that R1a and R1b originated in or near Kurdistan; two of the Bronze Age samples from Armenia are R1b (RISE397 and RISE413).

Today, I want to present 6 haplotypes (ht1-6) I could discover in the Kurdish gene pool.

ht3
represents the "European" haplotype which correlates with lactose
tolerance. Individuals with "CT" or "TT" at rs4988235 (also called C/T-13910) are genetically lactose tolerant; at 23andme it is "AG" or "AA" (because MCM6 gene is in minus orientation but 23andme does not address it).
Interestingly,
13910T (rs4988235: "A" at 23andme) and 22018A (rs182549: "T" at
23andme) are strongly linked with one another, at least for ht3, the "European"
haplotype. However, this is not always the case. There is some literature about 22018A, see here, here, here, and here.
ht3 itself is derived from ht2, which only carries the 22018A
mutation. ht2 is fairly rare and does not provide lactase
persistence which explains why 22018A is strongly, but not completely
related to lactase persistence. The origin of the "European"
lactose persistence 13910T (rs4988235: "A" at 23andme) can be found in populations where the frequency of 22018A (ht2 + ht3) is higher than 13910T (ht3).

In Kurds (N=20) the frequency of 22018A is 8% (ht2 + ht3), the frequency of 13910T is 5% (ht3). Both, ht2 and ht3 are derived from ht1, which has a frequency of 20% among Kurds.

Raz et al., 2013 found that Iraqi Jews (N=96) have a frequency 8.3% for 22018A (ht2 + ht3) and 3.6% for 13910T (ht3), which fits quite well with the Kurdish results.

Find below the frequency of the six MCM6 haplotypes in the Kurdish gene pool:

ht1

ht2

ht3

ht4

ht5

ht6

20%

3%

5%

15%

10%

48%

Find below the six
haplotypes (ht1 - ht6) identified in the Kurdish gene pool (ht7 was
identified in the Denisova genome. The coverage of the Neanderthal
genome was too low to identify the haplotype.)

Bersaglieri et al., 2004 provided the frequency of both 22018A and 13910T in various populations showing that the frequency of 22018A (ht2 + ht3) is higher than 13910T (ht3) in Pakistan (excluding Kalash).

Summary:
ht2 (22018A only) is the ancestor of ht3 (22018A + 13910T). ht2 can be found among Kurds, Iraqi Jews and Pakistanis.

I suspect that lactase persistence is also present among a subgroup of ht6.